YHV68 is a Y-herpesvirus that infects murid rodents and can cause B cell lymphomas in inbred mice. We recently observed that YHV68 also induces a Kaposi's sarcoma-like tumor (murine KS) in CD8 deficient beta32-/- mice. These tumors contained spindle cells that formed slit-like vascular spaces containing red blood cells, an inflammatory infiltrate including lymphocytes and plasma cells, as well as PAS staining globules - all of which are characteristic of human KS. The association of a murine Y- herpesvirus with this lesion is particularly intriguing given the recent identification of a human Y-herpesvirus , KSHV (HHV8), in human KS. Two other primate y-herpes viruses have been detected in macaque retroperitoneal fibromatosis - a fibrovascular tumor with similarities to human KS that occurs in immunosuppressed animals. The association of several Y-herpes viruses with fibrovascular tumors suggests that they share common pathogenic mechanisms for tumor induction. YHV68 provides a tractable small animal model for addressing issues pertinent to the role of Y-herpes viruses in the development of KS-like lesions in immunocompromised hosts. We propose to characterize the role of YHV68 in the development of murine KS as follows: 1. Characterize murine KS in YHV68 infected mice: a. incidence and characteristics of murine KS in beta2-/- mice; b. pathologic and virologic characterization of murine KS lesions. 2. Identify and characterize YHV68 gene expression during latency and in YHV68-induced tumors: a. identify tumor and latency-associated YHV68 transcripts; b. characterize YHV68 gene expression in murine KS, lymphomas and latently infected cells in vivo 3. Generate and characterize YHV68 mutants in tumor and latency-associated genes: a. creation of viruses with null mutations; b. analysis of viruses with null mutations in vitro and in vivo.